Anti-cd39 antibody

Abstract

The present invention addresses the problem of obtaining a superior anti-CD39 antibody. Provided is an antibody or antigen-binding fragment capable of binding to CD39, comprising heavy chain CDRs 1-3 and light chain CDRs 1-3 each containing a specific amino acid sequence. This antibody may be a CD39-neutralizing antibody. This antibody may have an ability to inhibit the growth of malignant tumor.

1 . An antibody or antigen-binding fragment that binds to CD39, comprising:
 (a) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 1, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 2, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 3 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 4, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 5, and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 6;   (b) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 7, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 8, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 9 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 10, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 11, and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 12;   (c) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 13, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 14, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 15 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 16, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 17, and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 18;   (d) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 19, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 20, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 21 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 22, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 23 and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 24;   (e) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 25, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 26, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 27 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 28, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 29 and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 30;   (f) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 31, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 32, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 33 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 34, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 35 and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 36; or   (g) heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 37, heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 38, and heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 39 and light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 40, light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 41 and light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 42.   
     
     
         2 . The antibody or antigen-binding fragment according to  claim 1 , which inhibits CD39 activity. 
     
     
         3 . The antibody or antigen-binding fragment according to  claim 1 , which inhibits growth of malignant tumor cells. 
     
     
         4 . The antibody or antigen-binding fragment according to  claim 1 , which promotes cytotoxicity of immune cells. 
     
     
         5 . The antibody or antigen-binding fragment according to  claim 1 , which is a monoclonal antibody. 
     
     
         6 . The antibody or antigen-binding fragment according to  claim 1 , wherein the antibody is a mouse, chimeric, or humanized antibody. 
     
     
         7 . The antibody or antigen-binding fragment according to  claim 1 , wherein K D  (M) toward CD39 is 9.0×10 −9  or less. 
     
     
         8 . The antibody or antigen-binding fragment according to  claim 1 , which is a glycan-modified antibody. 
     
     
         9 . A polynucleotide or vector that encodes the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         10 . A cell comprising the polynucleotide or vector according to  claim 9 . 
     
     
         11 . A method for producing an antibody or antigen-binding fragment, comprising the step of growing the cell according to  claim 10 . 
     
     
         12 . A composition comprising the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         13 . A method of treating a malignant tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         14 . A method of inhibiting CD39 activity in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         15 . A method of promoting TNFα production by immune cells in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         16 . A method of promoting cytotoxicity in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         17 . A pharmaceutical composition comprising the antibody or antigen-binding fragment according to  claim 1 , wherein the antibody or antigen-binding fragment has an N-type glycan, and 40% or more of the N-type glycan in the pharmaceutical composition is free of core fucose. 
     
     
         18 . A method of treating a malignant tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen-binding fragment according to  claim 1  and an effective amount of a chemotherapeutic agent. 
     
     
         19 . (canceled) 
     
     
         20 . A kit comprising the antibody or antigen-binding fragment according to  claim 1 . 
     
     
         21 . A method of selectively removing CD39 hi  cells in a subject in need thereof, the method comprising administering to the subject an effective amount of an anti-CD39 antibody.